The ability of low levels of fluoride ions to protect teeth against the development of carious lesions is well known, although the mechanism by which the protective effect is exerted still is only poorly understood. It has been shown that fluoride can affect both the tooth enamel and the metabolism of acidogenic microorganisms in plaque. Our interest has been in the latter and we have shown, in the early phase of the investigation, that low levels (1-10 ppm) of fluoride affect various strains of oral streptococci to differing degrees. Both quantitative and qualitative differences were observed. It was suggested that such behavior of plaque in microorganisms might explain the variability of clinical responses to water fluoridation. However, the basis for the variation in response to fluoride among the strains remained unexplained. One of the difficulties was that it was not clear whether oral microorganisms were capable of taking up fluoride from their growth media, even though it had been shown that plaque can accumulate significant amounts of fluoride from water and other sources. We were able to demonstrate that microorganisms such Streptococcus sanguis, S. mutans and S. salivarius can accumulate fluoride against a concentration gradient and that the cells possess fluoride binders with different affinities for the anion. The patterns of binding appeared to be related to the metabolic sensitivities of the cells. It will be the purpose of this investigation to pursue this line of experimentation in order to arrive at a better understanding of the cellular events that accompany fluoride inhibition. More specifically, we will examine the mechanisms by which cells accumulate, bind and utilize fluoride. The methods to be used will involve the chromatographic separation and purification of proteins and specific enzymes as well as kinetic analyses of fluoride binding and inhibition. It is expected that the information to be gained from this study will be highly valuable from the basic science viewpoint and, furthermore, the concepts that will evolve could lead to more effective approaches for the delivery of fluoride.